Rapostlin Is a Novel Effector of Rnd2 GTPase Inducing Neurite Branching

Fujita, Hirotada; Katoh, Hironori; Ishikawa, Yukio; Mori, Kazutoshi; Negishi, Manabu

doi:10.1074/jbc.m208090200

Cited by 79 publications

(97 citation statements)

References 36 publications

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“…It has been suggested that this domain is a microtubule-targeting domain (16). Indeed, a previous study revealed that Rapostlin, a rat ortholog of human FBP17, partially localizes to microtubules (15). We therefore examined the localization of EGFP-tagged FBP17 in COS-1 cells (Fig.…”

Section: Fbp17 Forms Tubular Invaginations In Living Cells-mentioning

confidence: 99%

“…DISCUSSION We have demonstrated that FBP17 forms tubular invaginations when expressed in cultured cells. Although Rapostlin, a rat ortholog of human FBP17, partially localizes to microtubules when expressed in HeLa cells (15), FBP17 did not localize to any components of the cytoskeleton such as microtubules, intermediate filaments, and actin fibers (Supplementary Fig. 1).…”

Section: Fbp17-induced Tubular Invaginationmentioning

confidence: 99%

“…Rapostlin shares 93% amino acid identity with FBP17, indicating that FBP17 is likely to be an ortholog of Rapostlin. Like CIP4, Rapostlin partially localizes to microtubules via its N-terminal FCH domain (15). Although the FCH domain is thought to be a microtubule-targeting domain (16), we have previously shown that the FCH domain of Fer tyrosine kinase is not required for localization of Fer to microtubules (17).…”

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confidence: 99%

“…A CIP4 homolog, Rapostlin, consists of an N-terminal FCH domain, an RBD, and a C-terminal SH3 domain similar to CIP4. Rapostlin has been identified as an effector that binds to the Rho family GTPase Rnd2 (15). Rapostlin shares 93% amino acid identity with FBP17, indicating that FBP17 is likely to be an ortholog of Rapostlin.…”

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confidence: 99%

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A Novel Dynamin-associating Molecule, Formin-binding Protein 17, Induces Tubular Membrane Invaginations and Participates in Endocytosis

Kamioka

Fukuhara

Sawa

et al. 2004

Journal of Biological Chemistry

108

112

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Dynamin associates with a variety of SH3 domaincontaining molecules via a C-terminal proline-rich motif and takes part, with them, in endocytic processes. Here, we have investigated a new dynamin-associating molecule, formin-binding protein 17 (FBP17), involved in deforming the plasma membrane and in endocytosis. FBP17 formed tubular invaginations originating from the plasma membrane. Its N-terminal Fer/CIP4 homology domain, a coiled-coil domain, and a proline-rich motif were required for tubular invagination and self-assembly, by which tubular invagination might be induced. Using anti-FBP17 antibody, we detected positive immunoreactions in the testis that were restricted to the germ cells. We also detected FBP17 in the brain by immunoblotting and in situ hybridization. When COS cells expressing enhanced green fluorescent proteintagged FBP17 were incubated with fluorescently labeled transferrin, epidermal growth factor, and cholera toxin, these molecules co-localized with FBP17-induced tubular invaginations, suggesting that FBP17 is involved in dynamin-mediated endocytosis in both a clathrin-dependent and -independent manner. These observations therefore indicate that FBP17 interacts with dynamin and regulates endocytosis by forming vesicotubular structures.The plasma membrane changes its structure dynamically in response to a wide variety of extracellular stimuli that alter cell shape. Membrane extension, including the formation of filopodia and lamellipodia, is controlled by the Rho family GTPases Cdc42 and Rac, respectively (1). Rac and Cdc42 are involved in forming membrane protrusions essential for phagocytosis and macropinocytosis (2), whereas another GTPase, dynamin, has been implicated in producing membrane invaginations and vesicles from the plasma membrane (3).Dynamin is a multidomain GTPase; it consists of a GTPase domain followed by a central domain lacking homology to any other proteins, a pleckstrin homology domain, an effector domain, and a C-terminal proline-rich motif (4). Dynamin-1 (neuron-specific), dynamin-2 (ubiquitously expressed), and dynamin-3 (expressed only in the testis, brain, and lung), constitute the dynamin family (5-7). These proteins are essential for clathrin-dependent and also caveolae-mediated endocytosis (reviewed in Refs. 8 and 9). In addition, association of dynamin with Src homology 3 (SH3) 1 domain-containing molecules has been shown to modulate endocytosis since the Cterminal proline-rich motif provides an SH3 domain-binding site (10). The dynamin-binding molecules amphiphysin, endophilin, intersectin, and PACSIN/syndapin have been reported to be involved in modulating dynamin-dependent endocytosis (4, 11).Formin-binding protein 17 (FBP17) consists of an N-terminal Fer/Cdc42-interacting protein 4 (CIP4) homology (FCH) domain followed by the first coiled-coil domain, a proline-rich motif, the second coiled-coil domain, a Rho family proteinbinding domain (RBD), and a C-terminal SH3 domain. FBP17 was originally isolated as a molecule that binds to the prolinerich region of ...

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Section: Fbp17 Forms Tubular Invaginations In Living Cells-mentioning

confidence: 99%

Section: Fbp17-induced Tubular Invaginationmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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A Novel Dynamin-associating Molecule, Formin-binding Protein 17, Induces Tubular Membrane Invaginations and Participates in Endocytosis

Kamioka

Fukuhara

Sawa

et al. 2004

Journal of Biological Chemistry

108

112

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“…Therefore, we renamed Toca-1 as Toca-1S, and named the lon-ger variant as Toca-1L. We have previously reported that Rapostlin/formin-binding protein 17 (FBP17; hereafter referred to as Rapostlin), a Toca-1 paralog, also has two splicing variants with and without the insert region between the F-BAR/EFC domain and the HR1: RapostlinL and RapostlinS, respectively (11,17). The conserved splicing pattern suggests that the presence of the insert region may make a functional difference.…”

Section: Toca-1 Is Strongly Expressed In Brain-when We Performedmentioning

confidence: 99%

Regulation of Neuronal Morphology by Toca-1, an F-BAR/EFC Protein That Induces Plasma Membrane Invagination

Kakimoto¹,

Katoh

Negishi

2006

Journal of Biological Chemistry

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Actin reorganization is important for regulation of neuronal morphology. Neural Wiskott-Aldrich syndrome protein (N-WASP) is an important regulator of actin polymerization and also known to be strongly expressed in brain. Recently, Toca-1 (transducer of Cdc42-dependent actin assembly) has been shown to be required for Cdc42 to activate N-WASP from biochemical experiments. Toca-1 has three functional domains: an F-BAR/EFC domain at the N terminus, an HR1 at the center, and an SH3 domain at the C terminus. The F-BAR/EFC domain induces tubular invagination of plasma membrane, while Toca-1 binds both N-WASP and Cdc42 through the SH3 domain and the HR1, respectively. However, the physiological role of Toca-1 is completely unknown. Here we have investigated the neural function of Toca-1. Toca-1 is strongly expressed in neurons including hippocampal neurons in developing brain at early times. Knockdown of Toca-1 in PC12 cells significantly enhances neurite elongation. Consistently, overexpression of Toca-1 suppresses neurite elongation through the F-BAR/EFC domain with a membrane invaginating property, suggesting an implication of membrane trafficking in the neural function of Toca-1. In addition, knockdown of N-WASP, to our surprise, also enhances neurite elongation in PC12 cells, which is in clear contrast to the previous report that dominant negative mutants of N-WASP suppress neurite extension in PC12 cells. On the other hand, knockdown of Toca-1 in cultured rat hippocampal neurons enhances axon branching a little but not axon elongation, while knockdown of N-WASP enhances both axon elongation and branching. These results suggest that a vesicle trafficking regulator Toca-1 regulates different aspects of neuronal morphology from N-WASP.Actin reorganization is important for regulating morphology of various cells including neurons (1). Neurons extend axons during the early phase of neural development. In this process, growth cones at the growing tips of axons play a critical role by detecting the guidance cues and mediating motility. Neurons then form synaptic connections and form a complex neural network to function properly. Rho family GTPases are implicated in morphological changes of various cells by reorganizing actin cytoskeleton (1). Among them, Rho, Rac, and Cdc42 have been extensively investigated. In neurons, Rac and Cdc42 stimulate neurite extension, whereas Rho triggers growth cone collapse and neurite retraction.Wiskott-Aldrich syndrome protein (WASP) 3 family members play essential roles in actin polymerization and have been much studied as a link between Rho family and actin cytoskeleton (2). WASP family members are characterized by their C-terminal VCA region (for verprolin homology (V) region, cofilin-homology (C) region, and acidic (A) region). They bind to both G-actin through the V region and Arp2/3 complex through the CA region, and activate Arp2/3 complex. The activated Arp2/3 complex nucleates de novo actin filaments and forms branched actin filament network. Five WASP family members have been d...

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Rnd proteins: Multifunctional regulators of the cytoskeleton and cell cycle progression

2010

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Rnd3/RhoE has two distinct functions, regulating the actin cytoskeleton and cell proliferation. This might explain why its expression is often altered in cancer and by multiple stimuli during development and disease. Rnd3 together with its relatives Rnd1 and Rnd2 are atypical members of the Rho GTPase family in that they do not hydrolyse GTP. Rnd3 and Rnd1 both antagonise RhoA/ROCK-mediated actomyosin contractility, thereby regulating cell migration, smooth muscle contractility and neurite extension. In addition, Rnd3 has been shown to have a separate role in inhibiting cell cycle progression by reducing translation of cell cycle regulators, including cyclin D1 and Myc. We propose that Rnd3 could act as a tumour suppressor to limit proliferation, but when mutations bypass this activity of Rnd3, it can promote cancer invasion through its effects in the actin cytoskeleton.

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Rapostlin Is a Novel Effector of Rnd2 GTPase Inducing Neurite Branching

Cited by 79 publications

References 36 publications

A Novel Dynamin-associating Molecule, Formin-binding Protein 17, Induces Tubular Membrane Invaginations and Participates in Endocytosis

A Novel Dynamin-associating Molecule, Formin-binding Protein 17, Induces Tubular Membrane Invaginations and Participates in Endocytosis

Regulation of Neuronal Morphology by Toca-1, an F-BAR/EFC Protein That Induces Plasma Membrane Invagination

Rnd proteins: Multifunctional regulators of the cytoskeleton and cell cycle progression

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